PDF(Pubmed)
Abstract：
Gaucher disease (GD) is a lysosomal storage disorder caused by a deficiency in the GBA1-encoded enzyme, β-glucocerebrosidase. Enzyme replacement therapy is ineffective for neuronopathic Gaucher disease (nGD). High-dose ambroxol has been administered as an alternative treatment for a group of patients with nGD. However, little is known about the clinical indication and the long-term outcome of patients after ambroxol therapy. We herein report a case of a female patient who presented with a progressive disease of GD type 2 from 11 months of age and had the pathogenic variants of p.L483P (formerly defined as p.L444P) and p.R502H (p.R463H) in GBA1. A combined treatment of imiglucerase with ambroxol started improving the patient\'s motor activity in 1 week, while it kept the long-lasting effect of preventing the deteriorating phenotype for 30 months. A literature review identified 40 patients with nGD, who had received high-dose ambroxol therapy. More than 65% of these patients favorably responded to the molecular chaperone therapy, irrespective of p.L483P homozygous, heterozygous or the other genotypes. These results highlight the long-lasting effect of ambroxol-based chaperone therapy for patients with an expanding spectrum of mutations in GBA1.
摘要：
戈谢病（GD）是由GBA1编码的酶缺乏引起的溶酶体贮积症，β-葡糖脑苷脂酶。酶替代疗法对神经特发性戈谢病（nGD）无效。高剂量氨溴索已被用作一组nGD患者的替代治疗。然而,对氨溴索治疗后患者的临床指征和长期结局知之甚少.我们在此报告了一例女性患者，该患者从11个月大开始患有2型GD进行性疾病，并且具有p.L483P（以前定义为p.L444P）和p.R502H的致病变异（p。R463H)在GBA1中。在1周内，用氨溴索联合丙种糖酶治疗开始改善患者的运动活动，同时它保持了30个月预防表型恶化的持久效果。文献综述确定了40例NGD患者，曾接受大剂量氨溴索治疗的患者。超过65%的患者对分子伴侣疗法有良好的反应，无论p.L483P纯合，杂合或其他基因型。这些结果突出了基于氨溴索的伴侣疗法对GBA1突变谱不断扩大的患者的持久效果。
